The　epidermal　growth　factor　receptor　(EGFR)　has　become　an　important　target　protein　in　anticancer　drug　development.　Meanwhile,　peptide-Au　cluster　has　been　proposed　as　potential　targeted　nano-drug　assembled　by　targeting　peptide.　Here,　we　designed　and　synthesized　a　novel　peptide-Au　cluster　as　Au(10)Peptide(5)　to　target　to　EGFR.　We　found　Au(10)Peptide(5)　could　target　to　the　natural　binding　sites　of　all　EGFRs　at　membrane　in　both　active　and　inactive　states　by　molecular　simulations.　Its　targeted　ability　was　further　verified　by　the　co-localization　and　blocking　experiments.　We　also　study　the　configuration　modifications　of　both　active　and　inactive　EGFRs　after　binding　by　Au(10)Peptide(5).　For　active　EGFR,　the　absorbed　Au(10)Peptide(5)　might　replace　the　natural　ligand　in　EGFR　endocytosis　process.　Then,　the　peptide-Au　cluster　in　endochylema　could　inhibit　the　cancer　relating　enzyme　activity　including　thioredoxin　reductase1　(TrxR1)　and　induce　the　oxidative　stress　mediated　apoptosis　in　tumor　cells.　For　inactive　EGFR,　it　was　retained　in　inactive　state　by　Au(10)Peptide(5)　binding　to　inhibit　dimerization　of　EGFR　for　anticancer.　Both　pathways　might　be　applied　in　anticancer　drug　development　based　on　the　theoretical　and　experimental　study　here.　(C)　2018　Science　China　Press.　Published　by　Elsevier　B.V.　and　Science　China　Press.　All　rights　reserved.